Cells of neural origin (NG108-15) which carry opiate receptors and can be maintained indefinitely in culture are used to study the mechanism of action of morphine and morphine-like peptides (enkephalin, endorphin). These materials exert a receptor mediated dual regulation of adenylate cylase; a rapid inhibition of activity upon which is superimposed a subsequnt increase in the amount of total expressible enzyme activity. This homeostatic mechanism may account for tolerance to and dependence upon the opiates. The enkephalins were found to be much more potent than their presumed precursors, the endorphins as mediators of dual regulation. Some actions of morphine are neither stereo-specific nor mimicked by opioid peptides. These actions appear to be mediated by a different class of receptor which may play a role in dependence. BIBLIOGRAPHIC REFERENCES: Goldstein, A., Cox, B. M., Klee, W. A. and Nirenberg, M.: Endorphin from pituitary inhibits cyclic AMP formation in homogenates of neuroblastoma x glioma hybrid cells. Nature 265: 362-363, 1977. Iorio, M. A. and Klee, W. A.: Relationships between opiate receptor binding and analgetic properties of prodine-type compounds. J. Med. Chem. 20: 309-310, 1977.